PROJECT SUMMARY Myoelectric interface prosthetic devices are often lauded as the next great innovation for those living with amputations. These devices typically utilize efferent neuromuscular signals, but movements that occur are often simple, disjointed, and require a separate, independent control signal for each motion. Modern prosthetics also lack any appreciable afferent sensory input that would generate appropriate proprioception and tactile feedback, thus forcing the user to visualize the device with each movement. As such, these devices are often associated with significant mental fatigue and eventual abandonment up to 75% of the time, causing significant disability. To prevent device rejection, development of an ideal prosthetic interface allowing for motor control alongside sensory feedback is key. A variety of peripheral nerve interfaces have been developed, but their success has been restricted by a critical lack of high-fidelity electrodes that would allow for stable and effective integration of the interface with the prosthetic. A novel strategy to address this issue is through the use of high-density multi-channel carbon fiber electrodes implanted into a composite regenerative peripheral nerve interface (C-RPNI). The C-RPNI entails implanting a sensorimotor peripheral nerve into a construct composed of a segment of free muscle graft sutured to dermal skin graft with reinnervation of appropriate sensory and motor end organs. The C-RPNI thus serves as an amplification system for prosthetic devices to detect simultaneous efferent motor signals and produce afferent sensory information. Fine-wire electrodes are currently utilized to interface with these C-RPNIs, but they cause fibrotic reaction over time and are limited by their inability to interact with single motor and sensory units. Carbon fiber electrodes have previously demonstrated chronic use in brain tissue without evidence of fibrotic reaction while maintaining single neural unit signaling capabilities, making them the ideal electrode material for this proposal. The overall objective of this proposal is to facilitate a neural, closed-loop sensorimotor control system for prosthetic function that mimics that of the absent limb. The central hypothesis is that these micro-scale, high-density carbon fiber electrode arrays will allow for chronic recording of compound muscle action potentials (CMAPs) from individual motor units alongside providing simultaneous electrical stimulation to produce afferent compound sensory nerve action potentials (CSNAPs) from single sensory units. This central hypothesis will be tested through the pursuit of two aims utilizing rats as the study group: (1) integrate a functional, high-density carbon fiber electrode array in C-RPNIs; and (2) use an integrated carbon fiber electrode array to chronically record and stimulate electrophysiological signaling from the C-RPNI. Developing and achieving both of these aims would encourage further progress towards the development of the ideal neural, closed-loop prosthetic device that would provide those living with amputations more natural and intuitive limb function.